Diastolic dysfunction is the impaired ability of the left ventricle to fill at physiologic pressures, often resulting in a compensatory increase of atrial filling pressures to maintain the stroke volume. This condition is usually associated with increased stiffness of the heart wall. Echocardiography can provide the most comprehensive information on diastolic function of the heart by integrating a variety of measurements with the clinical information. The goals of the next grant cycle are to produce ultrasound apparatus and techniques for quantitative and noninvasive high temporal and spatial resolution biopsy-like measurement of myocardial mechanical properties, specifically the anisotropic visco-elastic moduli of the heart wall in vivo. The new method, which we call vibrometry, uses radiation pressure of a focused ultrasound beam to stimulate formation and propagation of shear waves along the appropriate axes within the region of interest. The velocity and dispersion of the shear wave is measured with pulsed Doppler, B-scan correlation, or our new Kalman method. Mathematical models for the propagation of the wave in the particular geometry being studied will be used to solve analytically or with advanced inverse finite element methods for relevant mechanical properties such as the anisotropic visco-elastic moduli. Models will be validated with independent in vitro and in vivo measurements. In preliminary investigations of phantoms and excised hearts the method has been shown to be capable of performing fast, accurate and noninvasive measurements of the elastic (mu1) and viscous (mu2) terms of the shear modulus along and across the myofibers of excised myocardium and striated muscle. The goals of this program will be achieved through four Specific Aims. Aim 1: In a sequential development of increasingly complex theories, we will derive the analytic mathematical relationships between harmonic or impulse radiation force at a point or line in the heart wall and the resulting nearby propagating wave displacements caused by the force. Aim 2: We will use harmonic and impulse radiation force methods to induce motion and high precision methods to measure the resulting dynamic strain versus time and space in phantoms and tissues to validate the inverse solutions developed in Aim 1. Aim 3: Theory and methods from Aims 1 and 2 will be tested in isolated perfused beating and non beating hearts. A commercial scanner will be modified to make vibrometry measurements. Aim 4: Vibrometry will be extended to closed chest pigs in anticipation of clinical application. Successful completion of this program will result in techniques and procedures for measuring mechanical heart wall properties in humans providing a tool for evaluating cardiac abnormalities associated with alterations in heart wall stiffness. [unreadable] [unreadable] [unreadable]